scholarly journals Molecular docking, molecular dynamics simulation, biological evaluation and 2D QSAR analysis of flavonoids from Syzygium alternifolium as potent anti-Helicobacter pylori agents

RSC Advances ◽  
2017 ◽  
Vol 7 (30) ◽  
pp. 18277-18292 ◽  
Author(s):  
Tirumalasetty Muni Chandra Babu ◽  
Sivarathri Siva Rajesh ◽  
Baki Vijaya Bhaskar ◽  
Savita Devi ◽  
Aluru Rammohan ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
Helicobacter Pylori ◽  
Biological Evaluation ◽  
Dynamics Simulation ◽  
Computational Approaches ◽  
Qsar Analysis ◽  
Inhibitory Activities ◽  
Urease Inhibitory ◽  
Syzygium Alternifolium

The present study was carried out with the specific aim to evaluate anti-Helicobacter pylori(Hp) and urease inhibitory activities of three flavonoids from Syzygium alternifolium through thein vitroand bio-computational approaches.

scholarly journals A Computational Approach with Biological Evaluation: Combinatorial Treatment of Curcumin and Exemestane Synergistically Regulates DDX3 Expression in Cancer Cell Lines

Biomolecules ◽  
2020 ◽  
Vol 10 (6) ◽  
pp. 857
Author(s):  
Shailima Rampogu ◽  
Seong Min Kim ◽  
Minky Son ◽  
Ayoung Baek ◽  
Chanin Park ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
Molecular Dynamics Simulation ◽  
Cell Lines ◽  
Cancer Progression ◽  
Biological Evaluation ◽  
Dynamics Simulation ◽  
Promising Target ◽  
Vitro Analysis ◽  
Combinatorial Treatment

DDX3 belongs to RNA helicase family that demonstrates oncogenic properties and has gained wider attention due to its role in cancer progression, proliferation and transformation. Mounting reports have evidenced the role of DDX3 in cancers making it a promising target to abrogate DDX3 triggered cancers. Dual pharmacophore models were generated and were subsequently validated. They were used as 3D queries to screen the InterBioScreen database, resulting in the selection of curcumin that was escalated to molecular dynamics simulation studies. In vitro anti-cancer analysis was conducted on three cell lines such as MCF-7, MDA-MB-231 and HeLa, which were evaluated along with exemestane. Curcumin was docked into the active site of the protein target (PDB code 2I4I) to estimate the binding affinity. The compound has interacted with two key residues and has displayed stable molecular dynamics simulation results. In vitro analysis has demonstrated that both the candidate compounds have reduced the expression of DDX3 in three cell lines. However, upon combinatorial treatment of curcumin (10 and 20 μM) and exemestane (50 μM) a synergism was exhibited, strikingly downregulating the DDX3 expression and has enhanced apoptosis in three cell lines. The obtained results illuminate the use of curcumin as an alternative DDX3 inhibitor and can serve as a chemical scaffold to design new small molecules.

scholarly journals Arylaminopropanone Derivatives as Potential Cholinesterase Inhibitors: Synthesis, Docking Study and Biological Evaluation

Molecules ◽  
2020 ◽  
Vol 25 (7) ◽  
pp. 1751
Author(s):  
Anna Hudcová ◽  
Aleš Kroutil ◽  
Renata Kubínová ◽  
Adriana D. Garro ◽  
Lucas J. Gutierrez ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
Quantum Mechanics ◽  
Cholinesterase Inhibitors ◽  
Docking Study ◽  
Biological Evaluation ◽  
Enzyme Assays ◽  
Ic50 Values ◽  
Inhibitory Activities ◽  
Dynamics Simulations

Neurodegenerative diseases in which the decrease of the acetylcholine is observed are growing worldwide. In the present study, a series of new arylaminopropanone derivatives with N-phenylcarbamate moiety (1–16) were prepared as potential acetylcholinesterase and butyrylcholinesterase inhibitors. In vitro enzyme assays were performed; the results are expressed as a percentage of inhibition and the IC50 values. The inhibitory activities were compared with reference drugs galantamine and rivastigmine showing piperidine derivatives (1–3) as the most potent. A possible mechanism of action for these compounds was determined from a molecular modelling study by using combined techniques of docking, molecular dynamics simulations and quantum mechanics calculations.

Synthesis and Molecular Simulation Studies of Mandelic Acid Peptidomimetic Derivatives as Aminopeptidase N Inhibitors

2020 ◽  
Vol 16 ◽  
Author(s):  
Jiawei Chen ◽  
Qiaoli Lv ◽  
Guogang Tu
Keyword(s):  
Molecular Simulation ◽  
Mandelic Acid ◽  
Critical Role ◽  
Binding Mode ◽  
Biological Evaluation ◽  
Binding Energies ◽  
Aminopeptidase N ◽  
Dynamics Simulation ◽  
Inhibitory Activities

Background: The aminopeptidase N (APN) over-expressed in tumor cells plays a critical role in angiogenesis which makes the development of APN inhibitors an attractive strategy for cancer research. Aims and Objectives: It is clinically significant to develop potential APN inhibitors for cancer treatment. Reported here are the design, synthesis, biological evaluation and molecular simulation of mandelic acid peptidomimetic derivatives as APN inhibitors. Materials and Methods: Analysis of the binding mode of bestatin to APN lead to the design and synthesis of mandelic acid peptidomimetic derivatives. APN inhibitory activities in vitro were evaluated by spectrophotometric method. The binding mode of the target compounds with the APN binding site was studied relying on docking studies, molecular dynamics simulation experiments and binding energies calculation. Results: The structures of target compounds were confirmed by IR, 1H-NMR and MS. All compounds exhibited different range of inhibitory ability with IC50 values lying in micromolar level. The compound 9m was found to be most potent as compared to other target derivatives. Molecular simulation revealed that ligand coordinating with the catalytic zinc ion is very important for inhibitory activities. Conclusion: The compound 9m might represent a promising scaffold for the further development of novel anti-cancer drugs.

scholarly journals Identification of Anti-SARS-CoV-2 Compounds from Food Using QSAR-Based Virtual Screening, Molecular Docking, and Molecular Dynamics Simulation Analysis

2021 ◽  
Vol 14 (4) ◽  
pp. 357
Author(s):  
Magdi E. A. Zaki ◽  
Sami A. Al-Hussain ◽  
Vijay H. Masand ◽  
Siddhartha Akasapu ◽  
Sumit O. Bajaj ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
Molecular Docking ◽  
Virtual Screening ◽  
Simulation Analysis ◽  
Qsar Model ◽  
Quantitative Structure Activity Relationship ◽  
Dynamics Simulation ◽  
Multilinear Regression ◽  
Qsar Analysis ◽  
Main Protease

Due to the genetic similarity between SARS-CoV-2 and SARS-CoV, the present work endeavored to derive a balanced Quantitative Structure−Activity Relationship (QSAR) model, molecular docking, and molecular dynamics (MD) simulation studies to identify novel molecules having inhibitory potential against the main protease (Mpro) of SARS-CoV-2. The QSAR analysis developed on multivariate GA–MLR (Genetic Algorithm–Multilinear Regression) model with acceptable statistical performance (R2 = 0.898, Q2loo = 0.859, etc.). QSAR analysis attributed the good correlation with different types of atoms like non-ring Carbons and Nitrogens, amide Nitrogen, sp2-hybridized Carbons, etc. Thus, the QSAR model has a good balance of qualitative and quantitative requirements (balanced QSAR model) and satisfies the Organisation for Economic Co-operation and Development (OECD) guidelines. After that, a QSAR-based virtual screening of 26,467 food compounds and 360 heterocyclic variants of molecule 1 (benzotriazole–indole hybrid molecule) helped to identify promising hits. Furthermore, the molecular docking and molecular dynamics (MD) simulations of Mpro with molecule 1 recognized the structural motifs with significant stability. Molecular docking and QSAR provided consensus and complementary results. The validated analyses are capable of optimizing a drug/lead candidate for better inhibitory activity against the main protease of SARS-CoV-2.

scholarly journals Design, Synthesis, Biological Evaluation, and Molecular Modeling of 2-Difluoromethylbenzimidazole Derivatives as Potential PI3Kα Inhibitors

Molecules ◽  
2022 ◽  
Vol 27 (2) ◽  
pp. 387
Author(s):  
Xiangcong Wang ◽  
Moxuan Zhang ◽  
Ranran Zhu ◽  
Zhongshan Wu ◽  
Fanhong Wu ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
Molecular Docking ◽  
Molecular Modeling ◽  
3D Qsar ◽  
Binding Mode ◽  
Biological Evaluation ◽  
Field Analysis ◽  
Dynamics Simulation ◽  
Comfa Model ◽  
Qsar Models

PI3Kα is one of the potential targets for novel anticancer drugs. In this study, a series of 2-difluoromethylbenzimidazole derivatives were studied based on the combination of molecular modeling techniques 3D-QSAR, molecular docking, and molecular dynamics. The results showed that the best comparative molecular field analysis (CoMFA) model had q2 = 0.797 and r2 = 0.996 and the best comparative molecular similarity indices analysis (CoMSIA) model had q2 = 0.567 and r2 = 0.960. It was indicated that these 3D-QSAR models have good verification and excellent prediction capabilities. The binding mode of the compound 29 and 4YKN was explored using molecular docking and a molecular dynamics simulation. Ultimately, five new PI3Kα inhibitors were designed and screened by these models. Then, two of them (86, 87) were selected to be synthesized and biologically evaluated, with a satisfying result (22.8 nM for 86 and 33.6 nM for 87).

scholarly journals An Analysis Based on Molecular Docking and Molecular Dynamics Simulation Study of Bromelain as Anti-SARS-CoV-2 Variants

2021 ◽  
Vol 12 ◽  
Author(s):  
Trina Ekawati Tallei ◽  
Fatimawali ◽  
Afriza Yelnetty ◽  
Rinaldi Idroes ◽  
Diah Kusumawaty ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
Molecular Docking ◽  
Molecular Dynamics Simulation ◽  
Three Dimensional ◽  
Md Simulations ◽  
Inhibitory Effect ◽  
Dynamics Simulation ◽  
Novel Coronavirus

The rapid spread of a novel coronavirus known as SARS-CoV-2 has compelled the entire world to seek ways to weaken this virus, prevent its spread and also eliminate it. However, no drug has been approved to treat COVID-19. Furthermore, the receptor-binding domain (RBD) on this viral spike protein, as well as several other important parts of this virus, have recently undergone mutations, resulting in new virus variants. While no treatment is currently available, a naturally derived molecule with known antiviral properties could be used as a potential treatment. Bromelain is an enzyme found in the fruit and stem of pineapples. This substance has been shown to have a broad antiviral activity. In this article, we analyse the ability of bromelain to counteract various variants of the SARS-CoV-2 by targeting bromelain binding on the side of this viral interaction with human angiotensin-converting enzyme 2 (hACE2) using molecular docking and molecular dynamics simulation approaches. We have succeeded in making three-dimensional configurations of various RBD variants using protein modelling. Bromelain exhibited good binding affinity toward various variants of RBDs and binds right at the binding site between RBDs and hACE2. This result is also presented in the modelling between Bromelain, RBD, and hACE2. The molecular dynamics (MD) simulations study revealed significant stability of the bromelain and RBD proteins separately up to 100 ns with an RMSD value of 2 Å. Furthermore, despite increases in RMSD and changes in Rog values of complexes, which are likely due to some destabilized interactions between bromelain and RBD proteins, two proteins in each complex remained bonded, and the site where the two proteins bind remained unchanged. This finding indicated that bromelain could have an inhibitory effect on different SARS-CoV-2 variants, paving the way for a new SARS-CoV-2 inhibitor drug. However, more in vitro and in vivo research on this potential mechanism of action is required.

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